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10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents

10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with...

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Autores principales: Morak-Młodawska, Beata, Pluta, Krystian, Latocha, Małgorzata, Jeleń, Małgorzata, Kuśmierz, Dariusz, Suwińska, Kinga, Shkurenko, Aleksander, Czuba, Zenon, Jurzak, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691808/
https://www.ncbi.nlm.nih.gov/pubmed/31307242
http://dx.doi.org/10.1080/14756366.2019.1639695
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author Morak-Młodawska, Beata
Pluta, Krystian
Latocha, Małgorzata
Jeleń, Małgorzata
Kuśmierz, Dariusz
Suwińska, Kinga
Shkurenko, Aleksander
Czuba, Zenon
Jurzak, Magdalena
author_facet Morak-Młodawska, Beata
Pluta, Krystian
Latocha, Małgorzata
Jeleń, Małgorzata
Kuśmierz, Dariusz
Suwińska, Kinga
Shkurenko, Aleksander
Czuba, Zenon
Jurzak, Magdalena
author_sort Morak-Młodawska, Beata
collection PubMed
description 10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced (1)H and (13)C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine).
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spelling pubmed-66918082019-08-23 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents Morak-Młodawska, Beata Pluta, Krystian Latocha, Małgorzata Jeleń, Małgorzata Kuśmierz, Dariusz Suwińska, Kinga Shkurenko, Aleksander Czuba, Zenon Jurzak, Magdalena J Enzyme Inhib Med Chem Research Paper 10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced (1)H and (13)C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine). Taylor & Francis 2019-07-16 /pmc/articles/PMC6691808/ /pubmed/31307242 http://dx.doi.org/10.1080/14756366.2019.1639695 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Morak-Młodawska, Beata
Pluta, Krystian
Latocha, Małgorzata
Jeleń, Małgorzata
Kuśmierz, Dariusz
Suwińska, Kinga
Shkurenko, Aleksander
Czuba, Zenon
Jurzak, Magdalena
10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title_full 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title_fullStr 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title_full_unstemmed 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title_short 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
title_sort 10h-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691808/
https://www.ncbi.nlm.nih.gov/pubmed/31307242
http://dx.doi.org/10.1080/14756366.2019.1639695
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